PMID- 22265821
OWN - NLM
STAT- MEDLINE
DCOM- 20120625
LR  - 20161125
IS  - 1872-9754 (Electronic)
IS  - 0197-0186 (Linking)
VI  - 60
IP  - 3
DP  - 2012 Feb
TI  - Matrix metalloproteinase-3 is activated by HtrA2/Omi in dopaminergic cells: 
      relevance to Parkinson's disease.
PG  - 249-56
LID - 10.1016/j.neuint.2012.01.001 [doi]
AB  - Dopaminergic neurons in the substantia nigra are particularly vulnerable, and 
      their degeneration leads to Parkinson's disease. We have previously reported that 
      matrix metalloproteinase-3 (MMP-3) activity is involved in dopaminergic 
      neurodegeneration by multiple mechanisms and that this requires activation of 
      MMP-3 from proMMP-3 by an intracellular serine protease. HtrA2/Omi is a 
      mitochondrial serine protease that has been shown in non-dopaminergic cells to 
      translocate into the cytosol where it triggers apoptosis. In the present study we 
      sought to determine whether HtrA2/Omi might cause activation of MMP-3 in 
      dopaminergic neuronal cells using CATH.a cell line. Mitochondrial stress induced 
      by rotenone led to MMP-3 activation and HtrA2/Omi translocation into the cytosol. 
      The MMP-3 activation involved HtrA2/Omi, because both pharmacological inhibition 
      and siRNA-induced knockdown of HtrA2/Omi attenuated the activation induced by 
      rotenone or MPP+. Overexpression of mature HtrA2/Omi, but not mutant HtrA2/Omi, 
      resulted in MMP-3 activity increase and cell death. Addition of recombinant and 
      catalytically active HtrA2/Omi to lysate of untreated cells led to activation of 
      the endogenous MMP-3, and incubation of the HtrA2/Omi with recombinant proMMP-3 
      caused cleavage of proMMP-3 to a 48kD protein, corresponding to the active form, 
      which was accompanied by an increase in MMP-3 activity. Taken together, the data 
      indicate that HtrA2/Omi, which normally exists in the mitochondria, can cause 
      MMP-3 activation in the cytosol under a cell stress condition, which can 
      ultimately lead to demise of dopaminergic neuronal cells.
CI  - Copyright A(c) 2012 Elsevier Ltd. All rights reserved.
FAU - Shin, Eun Jung
AU  - Shin EJ
AD  - Department of Biochemistry and Molecular Biology, University of Ulsan College of 
      Medicine, Seoul 138-736, Republic of Korea.
FAU - Kim, Eun-Mee
AU  - Kim EM
FAU - Lee, Ji Ae
AU  - Lee JA
FAU - Rhim, Hyangshuk
AU  - Rhim H
FAU - Hwang, Onyou
AU  - Hwang O
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120111
PL  - England
TA  - Neurochem Int
JT  - Neurochemistry international
JID - 8006959
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (TRA2B protein, human)
RN  - 0 (Uncoupling Agents)
RN  - 0 (X-Linked Inhibitor of Apoptosis Protein)
RN  - 03L9OT429T (Rotenone)
RN  - 170974-22-8 (Serine-Arginine Splicing Factors)
RN  - 63231-63-0 (RNA)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Blotting, Western
MH  - Cell Death
MH  - Cytosol/drug effects/enzymology
MH  - Dopaminergic Neurons/*enzymology
MH  - Enzyme Activation/physiology
MH  - Humans
MH  - Immunohistochemistry
MH  - L-Lactate Dehydrogenase/analysis/metabolism
MH  - Matrix Metalloproteinase 3/*metabolism
MH  - Mitochondria/drug effects/enzymology
MH  - Nerve Tissue Proteins/antagonists & inhibitors/*genetics/*physiology
MH  - Parkinson Disease/*enzymology
MH  - RNA/biosynthesis/genetics
MH  - RNA, Small Interfering/genetics
MH  - RNA-Binding Proteins/antagonists & inhibitors/*genetics/*physiology
MH  - Real-Time Polymerase Chain Reaction
MH  - Rotenone/pharmacology
MH  - Serine-Arginine Splicing Factors
MH  - Silver Staining
MH  - Subcellular Fractions/metabolism
MH  - Transfection
MH  - Uncoupling Agents/pharmacology
MH  - X-Linked Inhibitor of Apoptosis Protein/metabolism
EDAT- 2012/01/24 06:00
MHDA- 2012/06/26 06:00
CRDT- 2012/01/24 06:00
PHST- 2011/08/15 00:00 [received]
PHST- 2011/12/19 00:00 [revised]
PHST- 2012/01/03 00:00 [accepted]
PHST- 2012/01/24 06:00 [entrez]
PHST- 2012/01/24 06:00 [pubmed]
PHST- 2012/06/26 06:00 [medline]
AID - S0197-0186(12)00002-2 [pii]
AID - 10.1016/j.neuint.2012.01.001 [doi]
PST - ppublish
SO  - Neurochem Int. 2012 Feb;60(3):249-56. doi: 10.1016/j.neuint.2012.01.001. Epub 
      2012 Jan 11.